生物信息学分析肝癌干细胞中致瘤基因表达的差异

Bioinformatics analysis of differentially expressed oncogenes in liver cancer stem cells

背景:研究认为,肝癌干细胞中致瘤基因表达与肝癌的发生、发展具有一定的关系,但目前尚缺乏对生物信息学和机制的研究。目的:对于肝癌干细胞相关的致瘤性差异基因进行筛选,并对其进行生物信息学分析。方法:将人肝癌细胞株Hep G2作为肝癌干细胞的细胞工具制备总RNA并进行荧光标记,使用基因芯片进行杂交试验,将获得的mR NA表达谱进行筛选后获得差异性m RNAs,利用生物信息学进行GO注释和Pathway注释分析。结果与结论:芯片杂交实验的检出率为73.21%,说明杂交试验是成功的;实验共有38 342个m RNA被发现,进一步分析后,筛选差异性表达基因1 236个(P<0.05,fold change≥2),其中上调和下调表达基因的数量分别为599和637个(P<0.05);表达差异基因的生物学功能主要涉及到了组蛋白的H4乙酰化,细胞的有丝分裂以及增殖、细胞相关蛋白质的合成以及分解、染色体的分离、细胞的分化以及凋亡、信号的转导、营养物质的运输、转录;Pathway注释主要涉及细胞因子介导的炎症信号通路、Wnt信号通路、Hedgehog通路以及Notch通路、TGF-Beta和Jak-STAT等。结果证实,肝癌干细胞中的差异表达基因与肝癌的发生有关,也可能参与信号通路的调控,这可为肝癌的治疗提供一种新靶点。

BACKGROUND： Studies have suggested that oncogene expression in liver cancer stem cells has a certain relationship with the occurrence and development of liver cancer, but there is still a lack of research on bioinformatics and mechanisms. OBJECTIVE： To identify differentially expressed genes in liver cancer stem cells and to analyze these genes by bioinformatics. METHODS： The human hepatoma cell line Hep G2 was the cell tool of liver cancer stem cells to prepare total RNA, and fluorescent labeling experiment was conducted. Using gene chips hybridization, m RNA expression profiles were obtained and were screened, and then differentially expressed m RNAs were obtained, GO and Pathway annotations were analyzed using bioinformatics. RESULTS AND CONCLUSION： The detection rate was 73.21% for hybridization experiment, indicating the hybridization experiment is successful. In this study, a total of 38 342 mR NA were found, and after further analysis, 1 236 differentially expressed genes were screened（P〈0.05, fold change ≥ 2）, including 599 up-regulated and 637 down-regulated genes, respectively（P〈0.05）. Biological functions of differentially expressed genes were mainly involved in the histone H4 acetylation, cell mitosis and proliferation, synthesis and decomposition of cell-associated proteins, chromosome segregation, cell differentiation and apoptosis, signal transduction, as well as nutrient transportation and transcription. Pathway annotations were mainly related to cytokine-mediated inflammatory signaling pathway, Wnt signaling pathway, Hedgehog and Notch signaling pathways, TGF-Beta, Jak-STAT and so on. These results demonstrate that differentially expressed genes in liver cancer stem cells are related to the occurrence of liver cancer, and may be involved in the regulation of signaling pathways, which provides a new target for the treatment of liver cancer.